People with schizophrenia have two- to three-times the mortality risk of the general population. This is primarily due to their unusually high rates o cigarette smoking, as well as other cardiovascular risk factors such as physical inactivity, obesity, high blood cholesterol and diabetes. Effective smoking treatments are needed to reduce morbidity and mortality in this population. Over a dozen experimental studies indicate that walking and other forms of exercise acutely reduce cigarette craving, nicotine withdrawal symptoms and smoking behavior in non-psychiatric smokers. However, the effects of acute exercise on smoking measures have not been studied in smokers with schizophrenia. The primary aim of this NIH Exploratory/Developmental (R21) Research Grant application is to investigate the acute effects of exercise, compared to a passive control condition, on subjective and behavioral smoking measures in smokers with schizophrenia. As episodic craving following exposure to smoking cues is associated with relapse during quit attempts, the secondary aim is to investigate whether exposure to smoking cues alters the ability of exercise to reduce cigarette craving and other smoking measures. The tertiary aim is to investigate whether factors known to moderate responses to smoking cessation medications (gender, antipsychotic medication type, intention to quit smoking) moderate the effects of exercise on smoking measures. This study will use a within-subjects, repeated-measures design, in which participants will undergo 1 practice session followed by 4 experimental sessions: (1) smoking cues followed by exercise, (2) smoking cues followed by passive activity, (3) neutral cues followed by exercise, (4) neutral cues followed by passive activity. Outcome measures include cigarette craving, nicotine withdrawal symptoms, mood and smoking behavior. If the results of this study indicate that walking acutely reduces craving and smoking in smokers with schizophrenia, the next step in this research would be to test the effectiveness of a smoking cessation intervention that incorporates exercise bouts as a behavioral strategy for improving smoking cessation rates in this population. PUBLIC HEALTH RELEVANCE: There is an unusually high rate of cigarette smoking among people with schizophrenia and correspondingly high rates of smoking-related morbidity and mortality in these patients. The aim of this project is to examine, under laboratory conditions, whether exercise reduces cigarette craving, nicotine withdrawal symptoms and smoking behavior in smokers with schizophrenia. If so, the next step in this research would be to examine the effectiveness of a smoking cessation intervention that incorporates exercise bouts as a behavioral strategy for reducing cigarette craving and smoking in smokers with schizophrenia.